BISPHOSPHONATES IN PROPHYLAXIS OF SKELETAL-RELATED ADVERSE EVENTS IN PATIENTS WITH CASTRATION-REFRACTORY PROSTATE CANCER

Prostate cancer (PC) is one of the most urgent problems of modern oncourology. Morbidity and mortality from this disease in theRussian Federationin recent years has been steadily increasing. Including the number of patients with metastatic and refractory to castration therapy forms of the disease is increasing. Currently, the main method of treatment of patients with metastatic prostate cancer is palliative hormone therapy (HT). Patients who have progression of tumor process, with lingering castration levels of testosterone, transferred to the stage of so-called castrate-resistant prostate cancer (CRPC). The prognosis in this group of patients is extremely unfavorable, not only because of the progression of cancer, but of complications associated primarily with the presence of bone metastases. Prevention of development of serious complications such as pathological fractures, spinal cord compression is an extremely important issue. The article presents a review of studies, the sanctifying of the problem of prevention of development of bone complications in patients with CRPC. We resent the results of large studies, including those conducted in our country demonstrated the effectiveness zoedronic acid in patients with CRPC and the presence of bone metastases.

1. Zlokachestvennye novoobrazovanija v Rossii v 2014 g. (zabolevaemost' i smertnost'). Ed by A.D. Kaprin, V. V. Starinskii, G. V. Petrova. Moscow, 2016. Available at: http://www. demoscope.ru/weekly/2016/0685/biblio04.php (Accessed: 25.03.2016) (Russian).

2. Alekseyev B.Ya., Nyushko K. M. Hormonal therapy for prostate cancer. Cancer Urology. 2007; 3: 57–62. (Russian).

3. Rusakov I.G., Alekseyev B. Y., Nyushko K. M. Hormonal therapy with leuprorelin (Lucrin-depot®) in patients with prostate cancer. Cancer Urology. 2009; 5 (3): 56–60. (In Russ.) doi:10.17650/1726–9776–2009–5-3–56–60.

4. Nyushko K. M., Alekseev B. Y., Kalpinsky A. S., Kaprin A.D. Luteinizing hormone-releasing hormone antagonists in patients with prostate cancer. A standard approach and the results of innovative studies. Cancer Urology. 2014;10 (4):70–74. (In Russ.) doi:10.17650/1726–9776–2014–10–4-70–74.

5. Biriukov V. A., Kariakin A.O., Gorban' N. A., Minaeva N.G., Alekseev B.Ia., Niushko K. M., et al. Results of the Russian multicenter prospective observational study of docetaxel (Taxotere) in patients with metastatic castration-resistant prostate cancer. Onkologiya. Zhurnal imeni P. A. Gertsena. 2013; 1 (6): 36–40. (Russian).

6. Bystrov S. V., Nyushko K. M., Alekseev B.Ya. Tautaks (dotsetaksel) v lechenii gormonorefrakternogo raka predstatel'noi zhelezy. Effective Pharmacotherapy. 2011; 45: 16–21. (Russian).

7. Alekseev B.Ia., Niushko K. M. Possibilities of using abiraterone acetate in hormonal therapy in castration-resistant prostate cancer. Onkologiya. Zhurnal imeni P. A. Gertsena. 2012; 1: 70– 72. (Russian).

8. Harada M., Iida M., Yamaguchi M., Shida K. Analysis of bone metastasis of prostate adenocarcinoma in 137 autopsy cases. Adv Exp Mad Biol. 1992; 324: 173–182.

9. Alekseev B. Y., Kaprin A.D., Nyushko K. M. A Role of somatostatin analogues in the treatment of patients with hormone-refractory prostate cancer. Cancer Urology. 2011;7 (2):84–87. (In Russ.) DOI:10.17650/1726–9776–2011–7-2–84–87. (Russian).

10. Alekseev B.Ia., Niushko K. M. Role of somatostatin analogues in the treatment of patients with castration-refractory prostate cancer. Onkologiya. Zhurnal imeni P. A. Gertsena. 2012; 2: 100– 102. (Russian).

11. Kaprin A.D., Alekseev B.Ya., Nyushko K. M., Kalpinskii A. S. Sovremennye podkhody k lekarstvennoi terapii bol'nykh metastaticheskim kastratsionno-refrakternym rakom predstatel'noi zhelezy. Farmateka. 2014; 8 (281): 35–39. (Russian).

12. Alekseev B.Ya., Nyushko K. M., Kalpinskii A. S., Kaprin A.D. Vozmozhnosti i kontseptsii lekarstvennoi terapii u bol'nykh kastratsionnorefrakternym rakom predstatel'noi zhelezy. Russkii meditsinskii zhurnal. 2014; 22 (17): 1234–1238. (Russian).

13. Alexeyev B.Ya., Nyushko K. M., Krasheninnikov A. A.. Somatostatin-analogs for the treatment of castration-resistant prostate cancer. Effective Pharmacotherapy. 2013; 6: 32–37. (Russian).

14. Nyushko K. M., Alekseev B.Ya. Gormonal'naya terapiya preparatom diferelin u bol'nykh rakom predstatel'noi zhelezy. Effective Pharmacotherapy. 2010; 29: 36–40. (Russian).

15. Nushko K.M., Kalpinskiy A. S., Kaprin A.D. Prevention of complications in castrate-refractory prostate cancer patients with bone metastases. Research'n Practical Medicine Journal. 2015; 2 (3): 76–81. (In Russ.) doi:10.17709/2409–2231–2015–2-3–76–81 (Russian).

16. Reddi A.H., Roodman D., Freeman C., Mohla S. Mechanisms of tumor metastases to the bone: challenges and opportunities. J of Bone and Mineral Research 2003; 18 (2): 190–194.

17. Russell R. Determinants of structure-function relationships among bisphosphonates. Bone. 2007; 40 (5): S21 S25.

18. Dunford J., Thompson K., Coxon F. P., Luckman S. P., Hahn F. M., Poulter C.D., et al. Structure-activity relationships for inhibition of farnesyl disphosphate synthase in vitro and inhibition of bone resorption in vivo by nitrogen-containing bisphosphonates. J Pharmacol Exp Ther. 2001; 296 (2): 235–242.

19. Rodan G., Fleisch H. Bisphosphonates: mechanism of actions. J Clin Invest. 1996; 97: 2692–2696.

20. Lehenkari P., Kellinsalmi M., Näpänkangas J., Ylitalo K. V., Mönkkönen J., Rogers M.J., et al. Further insight into mechanism of action of clodronate: inhibition of mitochondrial ADP/ATP translocase by a nonhydrolyzable, adenosine containing metabolite. Mol Pharmacol. 2002; 61 (5): 1255–1262.

21. Frith J., Monkkonen J., Auriola S., Mönkkönen H., Rogers M. The molecular mechanism of action of the antiresorptive and antiinflammatory drug clodronate: evidence for the formation in vivo of a metabolite that inhibits bone resorption and causes osteoclast and macrophage apoptosis. Arthritis Rheum. 2001; 44 (9): 2201–2210.

22. Bergstrom J., Bostedor R., Masarachia P., Reszka A., Rodan G. Alendronate is a specific, nanomolar inhibitor of farnesyl diphosphate synthase. Arch Biochem Biophys. 2000; 373 (1): 231–241.

23. Li E., Davis L. Zoledronic acid: a new parenteral bisphosphonate. Clin Ther. 2003; 25 (11): 2669–2708.

24. Green J. Chemical and biological prerequisites for novel bisphosphonate molecules: Results of comparative preclinical studies. Semin Oncol. 2001; 28 (2 Suppl 6): 4–10.

25. Benford H., McGowan N., Helfrich M., Nuttall M., Rogers M. Visualization of bisphosphonateinduced caspase 3 activity in apoptotic osteoclasts in vitro. Bone. 2001; 28 (5): 465–473.

26. Boissier S., Ferreras M., Peyruchaud O., Magnetto S., Ebetino F.H., Colombel M., et al. Bisphosphonates inhibit breast and prostate carcinoma cell invasion, an early event in the formation of bone metastases. Cancer Res. 2000;60 (11):2949–2954.

27. George R., Jeba J., Ramkumar G., Chacko A.G., Leng M., Tharyan P. Interventions for the treatment of metastatic extradural spinal cord compression in adults. Cochrane Database Syst Rev 2008; 8 (4): CD006716.

28. Black D. M., Delmas P.D., Eastell R., Reid I. R., Boonen S., Cauley J. A., et al. HORIZON Pivotal Fracture Trial. Once yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med. 2007; 356: 1809–1822.

29. Kulyayev Y. A., Grafov A. V., Falameyeva O. V., Khrapova Yu. V., Sadovoy M. A. Study of zoledronic acid preparation Rezoklastin FS 5 mg/6.25 ml (F Sintez CJSC) in patients with low bone mineral density. Effective Pharmacotherapy. 2013; 2 (38): 30–33. (Russian).